We propose developing a High Performance Bioreactor (HPBR) that uses a novel resonant-mixing motion of the fermentation vessel for agitation. The resonant-mixing motion has been demonstrated to cause significantly higher oxygen transport rates and better mixing than conventional methods. The HPBR overcomes state-of the-art fermentation technology limitations to supply adequate oxygen transfer and homogeneity necessary to utilize the biological potential of many organisms without creating high levels of shear. Phase I will demonstrate feasibility of the HPBR as a bioreactor and characterize its ability to transfer oxygen as a function of reactor processing variables, such as agitation intensity, operating frequency and gas-liquid volume. The effect(s) of these variables and their impact upon sustainable cell density with a fungal culture will be quantified. A prototype pharmaceutical fermenter will be built and fabricated in Phase II. The project will result in development of a new technology for growth of fungal, mammalian, plant, insect and other shear-sensitive systems. The commercial objective is to develop a product line of laboratory, modular, and large-scale fermentation systems. We will partner with an established firm that manufactures fermentation equipment to accomplish this goal. Development of the HPBR will result in the production of new and lower cost drugs. PROPOSED COMMERCIAL APPLICATION: The market for production units using advanced fermentation techniques is growing at a very rapid rate with current sales of modular units in the $30-$50 million per year range. Both Braun Biotech and ABEC report lengthening backlogs and strengthening pricing(1,2). In addition, drug companies are reporting that the current systems are technologically inadequate(3). This is a growing market where production technology is being left behind by the underlying research advances. Many companies are moving to large-scale fermentation of fungal, mammalian, insect, and plant cell cultures.(1) Development of the technology will result in demand at the laboratory scale(4).